Inhibition of progesterone receptor membrane component-1 exacerbates neonatal hypoxic-ischemic cerebral damage in male mice

Sun, Xiaoyu; Hu, Yuting; Zhou, Hui; Wang, Shang; Zhou, Chao; Lin, Li; Zhu, Taiyang; Jin, G.; Han, Jingjing; Zhou, Yan; Jia, Guanghong; Wang, Yuqiao; Zu, Jie; Shi, Hang; Yang, Xingxing; Zan, Kun; Wang, Jun; Fang, Hua

doi:10.1016/j.expneurol.2021.113893

Cited by 6 publications

(30 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another recent publication that assumes AG-205 is specific for PGRMC1, Sun et al [95] observed that AG-205 prevented neuronal resistance to hypoxic ischemia by preventing activation of NF-kB signaling and the BDNF/PI3K/AKT pathway. They concluded that PGRMC1 exerts a neuroprotective role following brain injury.…”

Section: Ag-205 Specificitymentioning

confidence: 99%

“…However, there was total disregard by Sun et al for the possibility that AG-205-mediated effects could operate independently of PGRMC1. As such, none of the published evidence demonstrates the claim of their title that inhibition of PGRMC1 aggravates cerebral ischemic damage caused by hypoxia [95]. Journal authors, reviewers and editors must clearly be more critical when assessing conclusions based upon the use of AG-205.…”

Section: Ag-205 Specificitymentioning

confidence: 99%

See 1 more Smart Citation

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Cahill¹

2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

The title usage of Unde venisti 'from where have you come' is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygeninduced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.

show abstract

Section: Ag-205 Specificitymentioning

confidence: 99%

Section: Ag-205 Specificitymentioning

confidence: 99%

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Cahill¹

2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…1,25 Moreover, the neurons expressing Reelin and DAB1 also express the progesterone-receptor-membrane-component-1 (PRMC1), which promotes neurogenesis and neuroprotection. 25,26 PRMC1-mediated neuroprotection of respiratory neurons damaged by autoimmunity might contribute to the sex disparity in COVID-19 mortality. 27 AIFM1 and SURF1 mutations cause Leigh syndrome, which is characterised by a subacute necrotising encephalopathy mainly affecting specifically the brainstem and closely resembling the COVID-19 acute necrotising encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

Anti-neuronal antibodies against brainstem antigens are associated with COVID-19

Lucchese¹,

Vogelgesang²,

Boesl³

et al. 2022

eBioMedicine

View full text Add to dashboard Cite

“…The HPA axis activity can affect memory, e.g., via stress signaling to the hippocampus [74] which involves glucocorticoid steroid hormones. PGRMC1 was originally identified under the synonym 'inner zone antigen' and a cytochrome P450-regulating protein associated with renal glucocorticoid steroidogenesis [75,76], and PGRMC1 is also located in gonads [77,78], pituitary [79], cortex, hypothalmus including hypothalamic nuclei involved in female reproduction, as well as in the hippocampus in neonatal and adult mice [55,80]. The latter is recognized as a central component in memory formation [81].…”

Section: Fig 2 the Hippocampus And Hypothalamus In Body Metabolism An...mentioning

confidence: 99%

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Cahill

2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

The title usage of Latin Quo vadis 'where are you going' extends the question Unde venisti from where 'did you come?' posed in the accompanying paper and extends consideration of how ancient eukaryotic and eumetazoan functions of progesterone receptor membrane component (PGRMC) proteins (PGRMC1 and PGRMC2 in mammals) could influence modern human health and disease. This paper attempts to extrapolate to modern biology in terms of extensions of hypothetical ancestral functional states from early eukaryotes and the last eumetazoan common ancestor (LEUMCA), to relativize human metabolic physiology and disease. As novel cell types and functional specializations appeared in bilaterian animals, PGRMC functions are hypothesized to have continued to be part of the toolkit used to develop new cell types and manage increasingly complex tasks such as nerve-gut-microbiome neuronal and hormonal communication. A critical role of PGRMC (as one component of a new eumetazoan genetic machinery) is proposed in LEUMCA endocrinology, neurogenesis, and nerve-gut communication with possible involvement in circadian nicotinamide adenine dinucleotide synthesis. This model would explain the contribution of PGRMC to metabolic and differentiation/behavioral changes observed in age-related diseases like diabetes, cancer and perhaps aging itself. Consistent with proposed key regulation of neurogenesis in the LEUMCA, it is argued that Alzheimer's disease is the modern pathology that most closely reflects the suite of functions related to PGRMC biology, with the 'usual suspect' pathologies possibly being downstream of PGRMC1. Hopefully, these thoughts help to signpost directions for future research.

show abstract

Inhibition of progesterone receptor membrane component-1 exacerbates neonatal hypoxic-ischemic cerebral damage in male mice

Cited by 6 publications

References 46 publications

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Anti-neuronal antibodies against brainstem antigens are associated with COVID-19

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Contact Info

Product

Resources

About